{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T14:44:12Z","timestamp":1786459452954,"version":"build-2736575974"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA018282"],"award-info":[{"award-number":["AA018282"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA007577"],"award-info":[{"award-number":["AA007577"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010519","name":"LSUHSC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010519","id-type":"DOI","asserted-by":"publisher"}]},{"name":"New Orleans, Biomedical Alcohol Research Training Program"},{"DOI":"10.13039\/100014517","name":"LBRN","doi-asserted-by":"publisher","award":["P20GM103424"],"award-info":[{"award-number":["P20GM103424"]}],"id":[{"id":"10.13039\/100014517","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Postbaccalaureate Research Education","award":["R25GM12189"],"award-info":[{"award-number":["R25GM12189"]}]},{"name":"COBRE","award":["P20GM121288-06"],"award-info":[{"award-number":["P20GM121288-06"]}]},{"name":"Translational Genomics Core"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Alcohol intake is a risk factor for the development of osteopenia. Ethanol perturbs gene expression in osteoblasts and osteoclasts and disrupts growth plate morphology. Hepatic metabolism of ethanol to acetate elevates concentrations of acetate in the circulation. We investigated whether acetate could, in part, mediate the toxicity of ethanol in bone and on chondrocyte differentiation. When ethanol and acetate were compared by gavage for 4 consecutive days, none of 11 selected genes involved in bone homeostasis were significantly affected by acetate, but acetate responses significantly correlated with ethanol responses. Intraperitoneal injection with acetate to transiently elevate serum acetate for 4 consecutive days significantly increased expression of 2 markers of osteoclast differentiation, calcitonin receptor (Calcr) and Ocstamp. Early chondrogenic differentiation of ATDC5 cells for 7\u2009days in vitro, characterized by aggrecan (Acan) and collagen 2a1 (Col2a1) mRNA expression and proteoglycan production, was inhibited by both 50\u2009mM ethanol and 5\u2009mM acetate. Ethanol effects were not blocked by the alcohol dehydrogenase inhibitor 4-methylpyrazole. 50\u2009mM ethanol retarded both ATDC5 cell growth and culture medium acidification. Inhibition of chondrogenic differentiation by 5\u2009mM acetate was associated with elevated phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2 and decreased expression of transcription factors Sox9 and Runx2. In acetate-exposed cells, blocking of ERK1 and ERK2 phosphorylation with Trametinib prevented further reduction of Acan and Col2a1 mRNA expression. We conclude that ethanol-derived acetate mediates at least part of the induction of Calcr and Ocstamp expression and that acetate mimics the effects of ethanol on early chondrogenic differentiation.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaf073","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T09:09:49Z","timestamp":1747818589000},"page":"181-195","source":"Crossref","is-referenced-by-count":3,"title":["Acetate derived from metabolism of ethanol affects gene expression in bone and contributes to delays in chondrogenic differentiation"],"prefix":"10.1093","volume":"207","author":[{"given":"Kim B","family":"Pedersen","sequence":"first","affiliation":[{"name":"Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, LA 70112,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6383-9602","authenticated-orcid":false,"given":"Cheyleann","family":"Del Valle Ponce de Leon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, LA 70112,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardy","family":"Hang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, LA 70112,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Ran","family":"Chen","sequence":"additional","affiliation":[{"name":"Arkansas Children\u2019s Nutrition Center, University of Arkansas for Medical Sciences , Little Rock, AR 72202,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E","family":"Randolph","sequence":"additional","affiliation":[{"name":"Center for Translational Pediatric Research, Arkansas Children's Research Institute , Little Rock, AR 72202,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovanny","family":"Zabaleta","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Oncology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center , New Orleans, LA 70112,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology & Parasitology, Louisiana State University Health Sciences Center , New Orleans, LA 70112,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology & Parasitology, Louisiana State University Health Sciences Center , New Orleans, LA 70112,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Denys","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, LA 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